Boceprevir Drug Combination for Hepatitis C Treatment in People With and Without HIV

This study has been terminated.

(Unable to complete enrollment due to newly approved treatment options.)

Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT01443923

First Posted: September 30, 2011

Last Update Posted: July 13, 2015

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
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- Standard treatment for the hepatitis C virus (HCV) is a combination of the drugs peg-IFN and ribavirin. However, this treatment is not very effective in people with a serious type of HCV (HCV genotype 1) and also in people who have human immunodeficiency virus (HIV) coinfection. Researchers want to add a new drug, boceprevir to see if it can improve treatment results in people with both HCV genotype 1 and HIV. Boceprevir used in combination with peg-IFN and ribavirin has been recently approved for the treatment of people with HCV genotype 1 infection only, and is currently being studied in those with HIV and HCV.

Objectives:

- To test boceprevir, peg-IFN, and ribavirin as a treatment for HCV genotype 1 in people with HCV monoinfection compared to those with both HIV and HCV infections.

Eligibility:

Individuals at least 18 years of age who have HCV genotype 1 infection, and have not received interferon treatment for HCV

Half of the study participants will also have HIV infection.

Design:

Participants will be screened with a medical history and physical exam. They will also have blood and urine tests.

Participants will also have heart and liver function tests, and answer questions about mood and depression.

Those in the study will receive ribavirin tablets to take twice a day, and peg-IFN to inject under the skin weekly.

Two weeks after starting treatment, participants will have blood tests to study the treatment.

Four weeks after starting treatment, participants will start taking boceprevir three times a day.

Participants will have regular study visits with blood samples and other tests. The length of therapy will depend on the level of virus detected in the blood at several clinic visits. Those who do not respond well to the medicines at 12 weeks will stop treatment. The full length of treatment is 48 weeks.

An Open Label, On-Treatment Trial to Assess the Effect of HIV-1 Coinfection on Therapeutic Responses Using Boceprevir, Peg-Interferon-alfa-2b and Ribavirin in HCV Genotype 1, IFN Treatment-Naive Subjects With or Without HIV-1

Proportion of Subjects Who Are Receiving HAART Who Remain With an HIV RNA & lt; 400 Copies/mL and Those With HIV RNA & gt; 400 Copies/mL at End of Treatment [ Time Frame: End of Treatment ]

Efficacy (SVR) Rates as Predicted by Viral Response at the End of the 4-week lead-in Therapy With PEG/RBV and Comparison Between HCV Monoinfected and HIV/HCV Coinfected Subjects [ Time Frame: 6 months post treatment ]

Chronic hepatitis C virus (HCV) infection is a major public health problem with an estimated 180 million people infected worldwide. In the United States, an estimated 4.1 million people are infected and HCV is the principal cause of death from liver disease and leading indication for liver transplantation. A combination of ribavirin (RBV) and pegylated interferon (peg-IFN) is the currently recommended therapy for chronic HCV infection. However, this therapy achieves viral clearance in only 19% to 52% of patients infected with HCV genotype 1 and 76% to 80% of patients infected with genotypes 2 and 3. Current therapy is also associated with a high incidence of adverse events and low cure rates in several populations. Novel therapies that do not rely on an interferon backbone will be required to enhance cure rates in various populations. Recent data show that adding an HCV serine protease inhibitor (such as boceprevir [BOC]) to peg-IFN and RBV results in HCV eradication rates of 70% to 80% among HCV-monoinfected subjects. However, whether human immunodeficiency virus (HIV)-infected subjects will have similar rates of response to triple combination therapy is presently not known. Previous data have suggested that HIV-infected patients with chronic HCV infection have much lower eradication rates to peg-IFN and RBV than HCV-monoinfected subjects. This study will explore whether HIV/HCV-coinfected subjects have a lower response rate to a BOC/peg-IFN/RBV regimen than HCV-monoinfected subjects. Participants who have chronic hepatitis C genotype 1 monoinfection (N=50) or coinfection with HIV-1 (N=50), and who are na(SqrRoot) ve to IFN-based HCV treatment, will receive combination therapy with BOC (800 mg three times a day, every 7 to 9 hours, with food), weekly peg-IFN alpha-2b (1.5 mcg/kg/week) and twice daily RBV (weight based) for a maximum of 44 weeks, after a 4-week lead-in of peg-IFN and RBV. BOC received recent FDA approval for treating HCV monoinfection in combination with peg-IFN and RBV, and the approved labeling will be followed in this study. The primary endpoint is comparative efficacy in HCV-monoinfected and HIV/HCV-coinfected subjects. Secondary endpoints include determination of host predictors for therapeutic response, emergence of resistance biomarkers, and early viral kinetics. The findings from this study will aid in the understanding of whether HIV infection affects HCV antiviral and host responses to combination therapy using BOC/peg-IFN alfa-2b/RBV.

Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

INCLUSION CRITERIA:

To be eligible for participation on this protocol, a participant must satisfy all of the following conditions:

Be greater than or equal to18 years old and have an identifiable primary care provider.

Have documented chronic HCV infection by demonstration of a positive test for hepatitis C antibody and HCV RNA of 2,000 IU/mL or greater.

Infected with HCV GT-1 virus.

If coinfected, have either documentation of HIV-1 infection by licensed enzyme-linked immunosorbent assay (ELISA) confirmed by a Western Blot or history of HIV RNA of 1,000 copies/mL or greater.

If coinfected, must meet one of the following prior to enrollment:

If on a stable non-NNRTI or non-PI antiretroviral regimen that HAS NOT changed within the past 6 months, must have an HIV-1 VL of less than 400 copies/mL for at least 3 months; or

If on a current antiretroviral regimen that HAS changed within the past 6 months, have an HIV-1 VL of less than 50 copies/mL for at least 3 months; or

Be a long-term nonprogressor as documented in the medica record.

Have histopathologic features consistent with chronic HCV infection at the time of enrollment. A liver biopsy within 3 years (36 calendar months) prior to screening may be used as the baseline biopsy. Participants can opt out of a liver biopsy if they had one more than 3 years prior and have a contraindication, such as receipt of chronic anticoagulation therapy. Participants with decompensated liver disease are excluded from the study.

Are na(SqrRoot) ve to prior IFN-based treatment for HCV.

Have CD4 cell counts greater than or equal to 100 cells/mm(3).

Willing to have genetic testing.

Not pregnant or breastfeeding. Serum pregnancy test must be negative at screening for female participants.

Agree not to become pregnant if a female of childbearing potential while on the study and for at least 6 months after stopping RBV. Because of the potential teratogenic effects of RBV treatment, subjects and their partners must remain abstinent or use two methods of birth control, which may be selected from the following list (oral contraceptive concentrations are decreased, and may not be effective when used during BOC treatment and, therefore, are not included in this list):

Surgical sterilization of either partner

Intrauterine device

Male or female condoms with or without a spermicide

Diaphragm, cervical cap, or sponge

Male participants who are not documented to be sterile must agree to either abstain from intercourse or consistently use a condom while their female partner (if applicable) agrees to use one of the appropriate medically accepted methods of birth control listed above from the date of screening until 6 months after the last dose of RBV.

Be able and willing to either learn to safely inject medication or find another person to inject the medication for him/her.

Be willing to allow storage of blood or tissue samples for future research.

Co-enrollment Guidelines:

Participants may be enrolled in other NIH protocols as long as the amount of research blood drawn does not exceed the acceptable NIH guidelines and the protocol does not include other experimental therapies (including expanded access/compassionate use of HIV antiretrovirals).

EXCLUSION CRITERIA:

A participant will be ineligible to participate on this study if any of the following criteria are met:

Use of other experimental therapies (including expanded access/compassionate use of HIV antiretrovirals) within 30 days or 5 half-lives (whichever is longer), prior to enrollment.

Current use of an efavirenz-based (or other NNRTI) or protease inhibitor HIV antiretroviral regimen.

Use of any of the following medications within 6 weeks prior to enrollment.

Alfuzosin (Uroxatral )

Alprazolam (Xanax )

Atorvastatin (Lipitor )

AZT or zidovudine (Retrovir )

Carbamazepine (Tegretol )

Cisapride (Propulsid )

Colchicine (Colcrys ) - If patient has renal or hepatic impairment.

DDI or didanosine (Videx )

d4T or stavudine (Zerit )

Delaviridine (Rescriptor )

Digoxin (Lanoxin )

Dihydroergotamine

Drosperinone (Yaz )

Efavirenz (Sustiva )

Ergonovine (Ergotrate )

Ergotamine (Cafergot )

Etravirine (Intelence )

Ganciclovir (Cytovene )

Immunosuppressive therapy (including oral steroids)

---Use of any use of any immunosuppressive therapy, including systemic steroids (prednisone equivalent of greater than 10 mg/day) for a duration of 6 weeks or more within 6 months prior to enrollment. Use of inhaled/nasal steroids should be avoided.

Has ingested silymarin (milk thistle), s-adenosylmethionine (SAM-e), glycyrrhizin, Sho-saiko-to (SST), or other herbal supplements that may be either liver beneficial or toxic, within 28 days prior to enrollment.

Has any systemic illness that will make it unlikely that the participant will be able to return for the required study visits.

Any condition that, in the opinion of the investigator, contraindicates participation in this protocol.

Exclusion of Children:

Because there are insufficient data regarding the safety and efficacy of BOC, PEG, or RBV in the pediatric population, children are excluded from this study.

Exclusion of Women:

Pregnancy: Pregnant women are excluded from this study because the effects of BOC, PEG, and RBV on the developing human fetus are unknown. Preclinical animal data indicate that the use of RBV treatment during pregnancy is potentially teratogenic.

Breastfeeding: Because there is an unknown but potential risk for adverse effects in nursing infants secondary to treatment of the mother with BOC, PEG, or RBV, breastfeeding women are excluded from this study.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01443923